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1647187 
Journal Article 
Forum original research communication - Hypoxia-mediated induction of herne oxygenase type I and carbon monoxide release from astrocytes protects nearby cerebral neurons from hypoxia-mediated apoptosis 
Imuta, N; Hori, O; Kitao, Y; Tabata, Y; Yoshimoto, T; Matsuyama, T; Ogawa, S 
2007 
Yes 
Antioxidants & Redox Signaling
ISSN: 1523-0864
EISSN: 1557-7716 
9 
5 
543-552 
17330989 
WOS:000245372300002 
To study a putative paracellular protective mechanism of astrocytes for neurons, immunohisitochemical analysis was performed in ischemic rat brain, which colocalized with the expression of heme oxygase-1 (HO-1) in astroglias surrounding dying TUNEL-positive neurons. As an in vitro paradigm for ischemia, cultured astrocytes were exposed to normobaric hypoxia (pO(2) approximate to 10 torr), which triggered marked increase in the expression of a 33 kDa stress protein, identified as HO-1. Induction of HO-1 message was observed within 4 h of hypoxia and peaked at 12 h, accompanied by an accelerated transcription of HO-1 message. Consistent with the induction of HO-1, a platelet bioassay revealed production of carbon monoxide by reoxygenated astrocytes. The presence of CO in the medium decelerated the hypoxia-mediated apoptotic type of cell death in cultured cerebral neurons via lowering the activity of caspase-3, a key enzyme regulating apoptotic cell death. This protection against apoptosis was likely mediated by CO-mediated increases in intracellular,cGMP, because exposure of hypoxic neurons to CO increased intracellular cGMP levels, and addition of cGMP analogue to hypoxic neuronal cultures suppressed caspase-3 activity and promoted neuronal survival.These data describe a potentially important paracellular pathway through which astrocytes may rescue nearby neurons from ischemic death.